This application responds to RFA: AT-02-002, 'Elucidation of the Underlying Mechanisms of Placebo Effect,' co-sponsored by 12 NIH institutes. Its key themes are non-pharmacological analgesia, consciousness, emotion, psychophysiology, somatic perception, individual differences, and time series analysis. The overall objectives of the proposed 4-year program of research are to validate a new theoretical approach to non-pharmacological analgesia through theory-driven, dynamic modeling grounded in structural equation reasoning. The work assumes a constructivist theoretical framework, which holds that the brain continuously constructs and revises a model of reality that includes both the external world and the body. When a noxious event occurs, the brain constructs pain as a part of ongoing consciousness from unconsciously activated schemata. Placebo analgesia reflects an altered construction of pain. A time series model provides a basis for evaluating predictions derived from constructivism in studies designed to create placebo analgesia. Two studies will investigate normal volunteers who undergo painful but harmless laboratory stimulation during a placebo manipulation that purports to relieve pain. The primary indicator for placebo analgesia is reduction in multivariate psychophysiological arousal to painful events. Study 1 (80 subjects) tests the hypotheses that greater expectancy for pain relief produces greater reduction in psychophysiological arousal to painful stimuli, and placebo analgesia is stronger when active rather than passive expectancy for pain relief can alter the subsequent construction of pain. Study 2 (125 subjects) focuses on placebo analgesia as a process that depends on somatic perception and expectancy, using a time series model. It tests the hypothesis that the task demand of producing a pain rating will decrease placebo analgesia by interfering feedback mechanisms that would normally revise expectancy. An additional purpose is to identify and explain individual differences in ability to benefit from a placebo. The proposed work will advance understanding of placebo analgesia by introducing and validating constructivism as a theoretical framework for placebo mechanisms, by examining the placebo effect as a dynamic process, and by contributing an unprecedented, testable explanatory time series model. [unreadable] [unreadable]